Medicines

Information
Bulletin
Vol. 14 No. 2

Vortioxetine (Brintellix) for depression

January 2016

DTG decision: Formulary Restricted

The Drugs and Therapeutics Group has included vortioxetine on the formulary as a restricted medicine. It should only be
1
used according to the NICE technology appraisal guidance (TA367) , which recommends vortioxetine as an option for
treating major depressive episodes in adults whose condition has responded inadequately to 2 antidepressants within
the current episode.
1

Vortioxetine is as effective as other antidepressants, but may have a better overall safety profile. Vortioxetine has procognitive effects and NICE suggests that it may be a valuable treatment option for people experiencing cognitive
1
dysfunction as part of their depression.
Clinicians wishing to prescribe vortioxetine must make an entry in the patients notes that clearly describes how the
restriction criteria are met.
What is it?
Vortioxetine is thought to work through a combination of two pharmacological modes of action: reuptake inhibition and
receptor activity. In vitro studies indicate that vortioxetine is an inhibitor of the serotonin transporter and also a 5-HT3, 5HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, and 5-HT1A receptor agonist. In vivo non-clinical
studies have demonstrated that vortioxetine modulates neurotransmission in several systems, including predominantly the
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serotonin but probably also the norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems.
How much does it cost?
Vortioxetine has a flat based pricing structure all
strengths are 27.72 for a 28 day supply.

Annual treatment cost for comparison

3

Vortioxetine 10mg OD
Mirtazapine 30mg OD
Venlafaxine 112.5mg BD
Venlafaxine MR TABLETS 225mg OD
Venlafaxine MR CAPSULES 225mg OD

What is the dose?

o Adults <65 years of age: 10 mg once daily
(starting and maintenance dose), increase to
20mg OD or reduce to 5mg OD depending on
individual patient response.
o Elderly 65 years of age: 5mg once daily. Increase if necessary to
10mg OD. Data is limited for doses >10mg in this age group.
o Children <18 years of age: no data.

Continue treatment for at least 6 months after symptoms have resolved.

per year (MIMS )

361.35
17.72
63.88
408.80
767.67

What tablet strengths are available?

Film coated tablets are available in
three strengths: 5mg, 10mg, and 20mg
2

How is it taken?
The tablets can be taken with or
Are there any contraindications or precautions?
without food.
Vortioxetine is contraindicated in anyone who is allergic to the active
substance or any of the excipients and in anyone taking a non-selective
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MAOI or moclobemide.
The following are included as precautions: suicide/suicidal thoughts or clinical worsening; seizures; serotonin syndrome;
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neuroleptic malignant syndrome; mania/hypomania; hyponatraemia; renal impairment; hepatic impairment. For more
detail refer to the manufacturers literature (SPC): http://www.medicines.org.uk/emc/medicine/30904
How does vortioxetine compare with other antidepressants?
Vortioxetine appears equally effective as other antidepressants but may have a better overall safety profile. It appears to
have no effect on body weight; no effect on pulse, blood pressure or any ECG parameter, including no effect on the QT
interval; it has not been associated with insomnia or somnolence; and the incidence of self-reported sexual dysfunction
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was low and similar to placebo.
What adverse effects does it cause?
As with all new drugs, vortioxetine is a black triangle
drug and all suspected adverse reactions should be reported to
the MHRA via the yellow card scheme (www.mhra.gov.uk/yellowcard).
Very common (=/>10%)

Nausea.

Common (>/=1/100 to <1/10)

Abnormal dreams, dizziness, diarrhoea, constipation, vomiting, pruritus.

Uncommon (>/=1/1000 to <1/100)

Flushing, night sweats.

Unknown

Serotonin syndrome.

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Are there any drug interactions?
Vortioxetine is extensively metabolised in the liver, primarily through oxidation catalysed by CYP2D6 and to a minor extent
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CYP3A4/5 and CYP2C9. It is therefore liable to a number of interactions :
Drug
Serotonergic medicines e.g.
tramadol, triptans
MAOIs, irreversible non-selective:
phenelzine, isocarboxazid,
tranylcycpromine

Effect
Caution. Increased risk of serotonin syndrome

Linezolid (MAOI, reversible nonselective)

Contraindicated due to risk of serotonin syndrome.

The manufacturer advises that if a combination of linezolid and vortioxetine proves necessary,
the minimum dose should be used with close monitoring for serotonin syndrome.

Moclobemide (MAO-A inhibitor,

reversible selective)

Contraindicated due to risk of serotonin syndrome.

The manufacturer advises that if a combination of moclobemide and vortioxetine proves
necessary, the minimum dose should be used with close monitoring for serotonin syndrome.

Selegiline and rasagaline (MAO-B

inhibitors, irreversible, selective)

Caution. A lower risk of serotonin syndrome is expected with selective MAO-B inhibitors than
with MAO-A inhibitors. None-the-less combining vortioxetine with MAO-B inhibitors such as
selegiline or rasagiline should be done cautiously, with close monitoring for serotonin syndrome.

CYP2D6 inhibitors e.g. bupropion,

quinidine, fluoxetine, paroxetine

Strong CYP2D6 inhibitors increase vortioxetine exposure and increase the risk of adverse
effects. A lower dose of vortioxetine should be considered.

CYP3A4 inhibitors and CYP2C9

inhibitors e.g. ketoconazole,
fluconazole
Broad CYP450 inducers e.g.
rifampicin, carbamazepine, phenytoin

No dose adjustment necessary.

Drugs that lower the seizure

threshold e.g. antidepressants,
antipsychotics, mefloquine,
bupropion, tramadol
Anticoagulants and antiplatelet drugs

Caution due to additive seizure threshold lowering effect.

Lithium and tryptophan.

Caution. Levels of lithium are not affected. However there are reports of enhanced effects when
antidepressants with serotonergic effect have been given together with lithium or tryptophan.

Smoking

No effect.

Contraindicated due to risk of serotonin syndrome.

Allow 14 days after stopping an MAOI before starting vortioxetine.
Allow 14 days after stopping vortioxetine before starting an MAOI.

Caution. Reduced vortioxetine exposure is possible. Dose adjustment according to response

may be necessary.

Caution. No pharmacokinetic interactions, however caution is recommended due to an

increased risk of bleeding as a result of a pharmacodynamic interaction.

How should patients be switched from their current antidepressant to vortioxetine?

FROM
Bupropion, mirtazapine, reboxetine, trazodone
Clomipramine, fluvoxamine
Fluoxetine
Citalopram, escitalopram, paroxetine, sertraline,
duloxetine, venlafaxine
Tricyclics (TCAs)
MAOIs
Moclobemide

SWITCH
TO VORTIOXETINE
Cross taper cautiously
Taper and stop then start low dose
Taper and stop, wait 4-7 days then start low dose
Cross taper cautiously starting with a low dose
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Halve dose, start vortioxetine, then slowly withdraw remainder of TCA

Taper and stop and wait for 2 weeks
Taper and stop and wait for 24 hours

How should vortioxetine be stopped?

Vortioxetine is not associated with discontinuation
symptoms, so it can be stopped abruptly without the need
to taper the dose.

References
1. NICE. Vortioxetine for treating major depressive episoes. Technology appraisal
guidance TA367, November 2015
2. Lundbeck Ltd. Vortioxetine Summary of Product Characteristics. Date of most
recent revision of the text: 17 June 2015
3. Monthly Index of Medical Spciaties (accessed online on 26.1.16 www.mims.co.uk)
4. Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry 12th
edition, Wiley 2015

Need more information?

For more detailed prescribing
information please refer to the SPC.
OR contact the Medicines Information
Service on 01865 904365 or email:
med.info@oxfordhealth.nhs.uk.